Search

Water scarcity is a persistent challenge, and in this case, the freshwater content in the air and water collection phenomena observed in nature provide ideas for fog harvesting. The fog-harvesting capabilities of natural spider silk have long attracted attention. Thus, researchers have undertaken significant efforts for the preparation of wettable biomimetic knotted fibers. However, the fragility of their chemical coating and the susceptibility of spun fibers to damage often present substantial challenges in the durability of fog harvesting equipment. Herein, from a bioengineering perspective, we review the improvement strategies for enhancing the mechanical properties of wettable biomimetic spider silk fibers based on the dense nanoconfined hydrogen-bond array crystalline regions and uniformly embedded amorphous regions of natural wettable spider silk fibers. These strategies aim to achieve high tensile strength, good fracture toughness, and corrosion resistance. Additionally, by incorporating UV inhibitors during spinning, the effects of sunlight can be mitigated or shielded, thereby greatly enhancing the mechanical durability of fog-harvesting devices under harsh realistic conditions.

Accurately ascertaining spatiotemporal distribution of pollution plume is critical for evaluating the effectiveness of remediation technologies and environmental risks associated with contaminated sites. This study concentrated on a typical Cr(VI) contaminated smelter being currently remediated using pump-and-treat (PAT) technology. Long-term on-site monitoring data revealed that two highly polluted regions with Cr(VI) concentrations of 162.9 mg/L and 234.5 mg/L existed within the contaminated site, corresponding to previous chromium slag yard and sewage treatment plant, respectively. The PAT technology showed significant removal performance in these highly polluted areas (>160 mg/L) after six months of pumping, ultimately achieving complete removal of the pollutants in these high-pollution areas. Numerical simulation results showed that although the current remediation scheme significantly reduced the Cr(VI) pollution degree, it did not effectively prevent the incursion of the pollution plume into the downstream residential area after 20 years. Additionally, an improved measure involving supplementary pumping wells was proposed, and its remediation effects were quantitatively evaluated. Results indicated that the environmental pollution risk of groundwater downstream could be effectively mitigated by adding pumping wells, resulting in a reduction of the pollution area by 20 % in the case of adding an internal well and 41 % with the addition of external wells after 20 years. The findings obtained in this study will provide an important reference and theoretical guidance for the reliability analysis and design improvement of the PAT remediation project., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Competing Interests: Declaration of interests JSJ reports grants and non-financial support from WHO, outside the submitted work. MW reports grants from the Wellcome Trust during the conduct of the study. All other authors declare no competing interests.

Receptor interacting protein kinase 1 (RIPK1) has emerged as a key regulatory molecule that influences the balance between cell death and cell survival. Under external stress, RIPK1 determines whether a cell undergoes RIPK-dependent apoptosis (RDA) or survives by activating NF-κB signaling. However, the role and mechanisms of RIPK1 on sunitinib sensitivity in renal cell carcinoma (RCC) remain elusive. In this study, we demonstrated that the O-linked β-N-acetylglucosamine modification (O-GlcNAcylation) of RIPK1 induces sunitinib resistance in RCC by inhibiting RDA. O-GlcNAc transferase (OGT) specifically interacts with RIPK1 through its tetratricopeptide repeats (TPR) domain and facilitates RIPK1 O-GlcNAcylation. The O-GlcNAcylation of RIPK1 at Ser 331 , Ser 440 and Ser 669 regulates RIPK1 ubiquitination and the formation of the RIPK1/FADD/Caspase-8 complex, thereby inhibiting sunitinib-induced RDA in RCC. Site-specific depletion of O-GlcNAcylation on RIPK1 affects the formation of the RIPK1/FADD/Caspase 8 complex, leading to increased sunitinib sensitivity in RCC. Our data highlight the significance of aberrant RIPK1 O-GlcNAcylation in the development of sunitinib resistance and indicate that targeting RIPK1 O-GlcNAcylation could be a promising therapeutic strategy for RCC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Neratinib (an active pharmaceutical ingredient [API]) is an irreversible pan-human epidermal growth factor receptor (HER) inhibitor used to treat HER2-positive breast cancer. The dosage form (marketed in the United States, China, Europe, and other regions) is a tablet for oral administration, and the brand product (NERLYNX) has patent protection for the crystalline neratinib maleate monohydrate form. This paper describes the product development using stable crystalline neratinib maleate anhydrous form, stability study, bioequivalence (BE) study of the products, and discussion of the adverse effects observed in the clinical study., (© 2024 John Wiley & Sons Ltd.)

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated genome editing system is widely used for targeted mutagenesis in a growing number of plant species. To streamline the screening process for mutants, especially those generated from low-efficiency editing events, there is a need for a rapid, cost-effective, and efficient method. Although several screening methods have been developed to process initial samples, these methods often tend to be time-consuming, expensive, or inefficient when dealing with larger sample sizes. Here we describe a simple, rapid, low-cost, and sensitive screening method for screening CRISPR/Cas9 mutants called PCR-Bsl I-associated analysis (PCR-BAA). This method requires only standard PCR and Bsl I restriction enzyme digestion, as well as agarose gel electrophoresis analysis. This method is particularly well suited for the efficient screening of mutants from larger populations of transformants. The simplicity, low cost, and high sensitivity of the PCR-BAA method make it particularly suitable for rapid screening of CRISPR/Cas9-induced mutants, especially those from low-efficiency editing events., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Wang Yiping reports financial support was provided by Yangzhou University. Wang Qiong reports was provided by Natural Science Foundation of Jiangsu Provinc. Wang Yiping, Liu Jinglan reports was provided by National Natural Science Foundation of China. Reports a relationship with that includes:. Has patent pending to. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Searching for lightweight and high-temperature stable electromagnetic wave-absorbing materials with broad absorbing bandwidth and high efficiency is of significance for applications in daily life and industry. Optimizing the dielectric properties of SiC nanowire aerogel by both compositional and structural designs is an efficient way to obtain simultaneous efficient wave-dissipation ability and good impendence matching and thus the desired properties. However, due to the complex effects of dielectric parameters on the wave-absorbing properties, rational design of high-performance electromagnetic wave-absorbing materials remains challenging. Herein, we propose a genetic algorithm-based approach to predict broadband and highly efficient electromagnetic wave-absorbing materials in a SiC@SiO 2 nanowire aerogel-based system. The obtained SiC@SiO 2 nanowire aerogels exhibit a gradient multilayered structure with a low dielectric outer layer, a medium layer with alternatively distributed electromagnetic wave transparent and attenuation layers, and an inner high attenuation layer, giving it a broadband electromagnetic wave-absorbing performance covering almost all the 2-18 GHz bandwidth and simultaneous high efficiency. The results show that the genetic algorithm-based approach is efficient in predicting high-performance electromagnetic wave-absorbing ceramic aerogels.

Ethnopharmacological Relevance: Wumei Wan (WMW), a traditional Chinese medicine prescription, has been proved to be effective in treating Colitis-associated colorectal cancer (CAC), but it has not been proven to be effective in different stages of CAC., Aim of the Study: The purpose of our study is to investigate the therapeutic effect and mechanism of WMW on the progression of CAC., Materials and Methods: Azioximethane (AOM) and dextran sulfate sodium (DSS) were used to treat mice for the purpose of establishing CAC models. WMW was administered in different stages of CAC. The presentative chemical components in WMW were confirmed by LC-MS/MS under the optimized conditions. The detection of inflammatory cytokines in the serum and colon of mice were estimated by qRT-PCR and ELISA. The changes of T cells and myeloid-derived suppressor cells (MDSCs) in each group were detected by flow cytometry. The metabolic components in serum of mice were detected by UPLC-MS/MS. Expression of genes and proteins were detected by eukaryotic transcriptomics and Western blot to explore the key pathway of WMW in preventing CAC., Results: WMW had significant effect on inhibiting inflammatory responses and tumors during the early development stage of CAC when compared to other times. WMW increased the length of mice's colons, reduced the level of IL-1β, IL-6, TNF-α in colon tissues, and effectively alleviated colonic inflammation, and improved the pathological damage of colon tissues. WMW could significantly reduce the infiltration of MDSCs in the spleen, increase CD4 + T cells and CD8 + T cells in the spleen of CAC mice, and effectively reform the immune microenvironment in CAC mice. Transcriptomics analysis revealed that 2204 genes had different patterns of overlap in the colon tissues of mice between control group, AOM + DSS group, and early administration of WMW group. And KEGG enrichment analysis showed that PI3K/Akt signaling pathway, ECM-receptor interaction, IL-17 signaling pathway, MAPK signaling pathway, pancreatic secretion, thermogenesis, and Rap1 signaling pathway were all involved. The serum metabolomics results of WMW showed that the metabolic compositions of the control group, AOM + DSS group and the early stage of WMW were different, and 42 differential metabolites with the opposite trends of changes were screened. The metabolic pathways mainly included pyrimidine metabolism, glycine, serine and threonine metabolism, tryptophan metabolism, and purine metabolism. And amino acids and related metabolites may play an important role in WMW prevention of CAC., Conclusion: WMW can effectively prevent the occurrence and development of CAC, especially in the initial stage. WMW can reduce the immune infiltration of MDSCs in the early stage. Early intervention of WMW can improve the metabolic disorder caused by AOM + DSS, especially correct the amino acid metabolism. PI3K/Akt signaling pathway was inhabited in early administration of WMW, which can regulate the amplification and function of MDSCs., Competing Interests: Declaration of competing interest All authors disclosed no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Pyroptosis, an inflammatory programmed cell death, has recently been found to play an important role in spinal cord injury (SCI). C-type lectin domain family 5 member A (CLEC5A), triggering receptor expressed on myeloid cells 1 (TREM1), and NLR-family CARD-containing protein 4 (NLRC4) have been reported to be associated with neuronal pyroptosis, but few studies have clarified their functions and regulatory mechanisms in SCI. In this study, CLEC5A, TREM1, and NLRC4 were highly expressed in lidocaine-induced SCI rat models, and their knockdown alleviated lidocaine-induced SCI. The elevation of pyroptosis-related indicators LDH, ASC, GSDMD-N, IL-18, caspase-1, and IL-1β levels in SCI rats was attenuated after silencing of CLEC5A, TREM1, or NLRC4. Lidocaine-induced decrease in cell viability and the elevation in cell death were partly reversed after CLEC5A, TREM1, or NLRC4 silencing. Lidocaine-mediated effects on the levels of LDH, ASC, GSDMD-N, IL-18, caspase-1, and IL-1β in lidocaine-induced PC12 cells were weakened by downregulating CLEC5A, TREM1, or NLRC4. CLEC5A could interact with TREM1 to mediate NLRC4 expression, thus accelerating neuronal pyroptosis, ultimately leading to SCI exacerbation. In conclusions, CLEC5A interacted with TREM1 to increase NLRC4 expression, thus promoting neuronal pyroptosis in rat SCI models, providing new insights into the role of neuronal pyroptosis in SCI., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Tan et al.)

Introduction: Gestational diabetes mellitus (GDM) is a common complication during pregnancy. The hyperglycemic stimulation of gestational diabetes inhibits the invasion of the placental trophoblast cells. Some studies have indicated that the senescence of trophoblast cells weakens their invasive capacity, while the mechanism of trophoblast cells senescence in GDM remain elusive., Methods: We performed western blotting and Immunohistochemical staining to investigate AT-Rich Interaction Domain 1A (ARID1A) expression in GDM placental tissues. 5 mM and 30 mM glucose treated HTR-8/SVneo cells to simulate normal glucose (NG) stress and high glucose (HG) stress. Cell proliferation capacity was investigated by CCK8 assay and cell cycle assay. SA-β-gal was used to detect cellular senescence. Chip-seq characterized the binding site of ARID1A to CDKN1A. In conjunction with bioinformatics analysis, co-immunoprecipitation assays, Chip-qPCR and luciferase reporter assays were performed to prove ARID1A recruits GATA2 to CDKN1A., Results: We found that ARID1A has a higher expression levels in GDM placental tissues compared to the control. ARID1A overexpression suppressed cell proliferation, induced cell cycle arrest and promoted cell senescence. Conversely the inhibition of ARID1A significantly rescues HG induced senescence of trophoblast cells. To further characterize the mechanism by which ARID1A regulate the transcription of CDKN1A, co-immunoprecipitation assays, Chip-qPCR and luciferase reporter assay indicate that ARID1A recruits GATA2 to regulate the transcriptional activity of CDKN1A., Discussion: Our study uncovers a ARID1A mediated regulatory mechanism in GDM trophoblast cell senescence and suggests that targeting the placental ARID1A might provide new diagnostic and therapeutic strategies for GDM., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interests., (Copyright © 2024. Published by Elsevier Ltd.)

Sodium-ion batteries (SIBs) have emerged as a promising alternative to lithium-ion batteries (LIBs) due to the abundant availability of sodium, lower costs, and comparable electrochemical performance characteristics. A thorough understanding of their performance features is essential for the widespread adoption and application of SIBs. Therefore, in this study, we investigate the output characteristics and electrochemical impedance spectroscopy (EIS) features of sodium-ion batteries (SIBs) under various states. The research results show that, unlike conventional lithium iron phosphate (LFP) batteries, SIBs exhibit a strong linear relationship between state of charge (SOC) and open-circuit voltage (OCV) across various SOC and temperature conditions. Additionally, the discharge capacity of the battery remains relatively stable within a temperature range of 15 °C to 35 °C; when the temperatures are outside this range, the available capacity of the sodium-ion battery reduces significantly. Moreover, the EIS profiles in the high-frequency region are predominantly influenced by the ohmic internal resistance, which remains largely unaffected by SOC variations. In contrast, the low-frequency region demonstrates a significant correlation between SOC and impedance, with higher SOC values resulting in reduced impedance, indicated by smaller semicircle radii in the EIS curves. This finds highlights that EIS profiling can effectively monitor SOC and state of health (SOH) in SIBs, offering a clear correlation between impedance parameters and the battery's operational state. The research not only advances our understanding of the electrochemical properties of SIBs but also provides a valuable reference for the design and application of sodium-ion battery systems in various scenarios.

Directed alterations of the enzyme's temperature adaptations, such as thermostability and optimal catalytic temperature (T opt ), are usually the way to go in order to meet the applications, however they are limited by the understanding between protein structure and function. Glutamate decarboxylase (GADs) is a common enzyme in the food industry. In this study, we identified and characterized three novel L-glutamate decarboxylases from psychrophilic microorganisms. Interestingly, the two enzymes (Gad Psy.Y/Gad Psy.F) showed significant differences in temperature adaptation. Through multiple sequence alignment and structural analysis, two potential regions that may affect the T opt and thermostability of the GAD, termed temperature adaptation modules (TAMs), were targeted. To validate the role of TAMs, we constructed mutants with bi-directional transplants of TAMs, which ultimately significantly altered the temperature adaptation of Gad Psy.Y and Gad Psy.F. Molecular dynamics simulations analysis demonstrated that the introduction and disruption of salt bridges in the mutant TAMs are crucial for this alteration. These findings deepen the understanding of the mechanisms of protein temperature adaptation and provide implications for protein engineering, while also offering advantageous enzymes to support the biosynthesis of GABA., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: The aim of this study was to detect trends and related factors in the functional dentition (FD) in 65- to 74-year-olds in Guangdong, China, while also assessing trends in education and income inequality factors., Materials and Methods: Three large-scale cross-sectional National Oral Health Surveys (NOHS), specifically NOHS II in 1995, NOHS III in 2005, and NOHS IV in 2015, were included. Post hoc stratification was weighted for 1038 participants aged 65 to 74years. Retaining teeth ≥ 20 teeth and retaining < 20 teeth was defined as functional dentition (FD) and nonfunctional dentition (NFD), respectively. Logistic regression models were established to assess related factors. Slope index of inequality (SII) and relative index of inequality (RII) were used to analyze inequality., Results: From NOHS II to IV, the FD proportion increased from 42.8 to 71.9%. Years of NOH, with caries, with periodontal pocket, high educational level, high income level, female, and those who had dental visits were associated with FD preservation. The education-related SII decreased from 0.44 to 0.20, and the income-related SII increased from 0.13 to 0.16., Conclusions: The FD proportion among 65- to 74-year-olds improved from 1995 to 2015. Years of NOHS, with caries, with periodontal pocket, high education level, and high income level were associated with higher FD proportion. Female and those who had dental visits were associated lower FD proportion. Social inequalities in FD persisted, especially economic-related inequalities. Public health policy support and respective interventions should be applied to increase FD retention., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Traditional Chinese medicine (TCM) is used to treat mycoplasma pneumonia (MP) in children with favorable treatment outcome in China. In the present study, we evaluated the clinical efficacy of TCM combined with azithromycin (AZM) for the treatment of MP among children, providing high evidence-based reference for clinical treatment., Method: We retrieved eligible randomized controlled trials (RCTs) from CQVIP, CNKI, WanFang, NSTL, PubMed, Embase, and Embase databases from January 2000 to November 2023. Data extraction and quality assessment of the enrolled studies were independently by two reviewers. Review Manager 5.3 was used for meta-analysis., Result: A total of 51 RCTs involving 5,799 children aged 1-14 enrolled. Meta-analysis demonstrated that TCM combined with AZM improved the cure rate (odds ratio [OR] = 2.34, 95% CI: 2.06 to 2.64) and the effective rate (OR = 5.21, 95% CI: 4.22 to 6.43), shorted the disappearance duration of cough (WMD = -1.62, 95% CI: -1.90 to -1.34), the duration of fever (WMD = -1.62, 95% CI: -1.96 to -1.29), and the disappearance time of lung rales (WMD = -1.15, 95% CI: -1.32 to -0.98), improved CRP levels (WMD = -2.06, 95% CI: -2.57 to -1.55), IL-6 levels (WMD = -1.92,95% CI: -2.51 to -1.34), and TNF-α levels (WMD = -1.59, 95% CI: -2.14 to -1.04), and reduced adverse reactions (OR = 0.37, 95% CI: 0.32 to 0.44)., Conclusion: TCM combined with AZM in the treatment of MP among children has favorable clinical efficacy and safety., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lyu, Fan, Li, Wang, Tian, Xu, Zhang and Wang.)

Rapid urbanization has exerted immense pressure on urban environments, severely constraining the growth of ancient trees. The growth of ancient trees is closely linked to the microbial communities in their rhizospheres, and studying their community characteristics may provide new insights into promoting the growth and rejuvenation of ancient trees. In this study, the rhizosphere soil and root systems of ancient Ginkgo biloba trees (approximately 200 years old) and adult G. biloba trees (approximately 50 years old) in Shanghai were selected as research subjects. Phospholipid fatty acid (PLFA) analysis and high-throughput sequencing were employed to investigate the diversity of microbial communities in the G. biloba rhizosphere. The results indicated that the 19 PLFA species selected to characterize the soil microbial community structure and biomass were present in the rhizosphere soil of both ancient and adult G. biloba trees. However, the total microbial biomass and the microbial biomass in the rhizosphere soil of ancient G. biloba were lower than the microbial biomass in the rhizosphere soil of adult G. biloba . The biomasses of Gram-negative bacteria (G - ), arbuscular mycorrhizal fungi (AMF), and protozoans (P) were significantly different. Total phosphorus, organic matter, and pH may be the key factors influencing the soil microbial community in the rhizosphere zone of ancient G. biloba . An in-depth study of AMF showed that the roots and rhizosphere soil of G. biloba contained abundant AMF resources, which were assigned to 224 virtual taxa using the MaarjAM reference database, belonging to four orders, ten families, and nineteen genera. The first and second most dominant genera were Glomus and Paraglomus , respectively. Archaeospora and Ambispora were more dominant in the rhizosphere than the roots. Furthermore, the abundance of live AMF was significantly higher in ancient G. biloba than in adult G. biloba . Therefore, future research should focus on the improvement of soil environmental characteristics and the identification and cultivation of indigenous dominant AMF in the rhizosphere of ancient G. biloba , aiming for their effective application in the rejuvenation of ancient trees.

Background: Diabetic nephropathy (DN) is a severe microvascular complication of diabetes characterized by inflammation, oxidative stress, and renal fibrosis. Asiaticoside (AC) exhibits anti-inflammatory, antioxidant, and anti-fibrotic properties, suggesting potential therapeutic benefits for DN. This study aimed to investigate the protective effects of AC against DN and elucidate the underlying mechanisms involving the nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) antioxidant pathway., Aim: To investigate the renoprotective effects of AC against DN and elucidate the role of the NRF2/HO-1 pathway., Methods: The effects of AC on high glucose (HG)-induced proliferation, inflammation, oxidative stress, and fibrosis were evaluated in rat glomerular mesangial cells (HBZY-1) in vitro . A streptozotocin-induced DN rat model was established to assess the in vivo impact of AC on renal injury, inflammation, oxidative stress, and fibrosis. The involvement of the NRF2/HO-1 pathway was examined using pharmacological inhibition studies in the cell model., Results: AC inhibited HG-induced HBZY-1 cell proliferation and significantly improved various indicators of DN in rats, including reduced body weight, and elevated blood glucose, serum creatinine, blood urea nitrogen, and 24-h urine protein. Both in vitro and in vivo studies demonstrated that AC decreased inflammation and oxidative stress by reducing interleukin (IL)-6, IL-8, tumor necrosis factor-alpha, reactive oxygen species, and malondialdehyde levels while increasing superoxide dismutase activity. Additionally, AC suppressed the expression of fibrogenic markers such as collagen I, collagen IV, and fibronectin. AC activated NRF2 expression in the nucleus and increased HO-1 and NAD(P)H dehydrogenase (Quinone) 1 protein expression in renal tissues and HG-induced HBZY-1 cells., Conclusion: AC improves DN by reducing inflammation, oxidative stress, and fibrosis through the activation of the NRF2/HO-1 signaling pathway. These findings not only highlight AC as a promising therapeutic candidate for DN but also underscore the potential of targeting the NRF2/HO-1 pathway in developing novel treatments for other chronic kidney diseases characterized by oxidative stress and inflammation., Competing Interests: Conflict-of-interest statement: Lan-Gen Zhuang has received research funding from the Natural Science Research Project of Anhui Educational Committee and the General project of Anhui Provincial Health and Construction Commission. Other authors declare that there are no conflicts of interest to disclose for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Anemia significantly contributes to the global disease burden, with its incidence potentially influenced by the trace metal content within the body., Objective: This study aims to examine the associations between trace metals and anemia risk, with a particular focus on investigating the potential mediating roles of iron status and inflammation in these associations., Methods: Five trace metals (Ni, Co, Mn, Se, and Mo) were examined in 1274 US adults, utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2017-2020. The individual and combined effects of these metals on anemia were assessed using logistic regression, quantile g-computation (QGC), and Bayesian kernel machine regression (BKMR). A sex-stratified analysis was conducted to discern any gender-specific susceptibilities. Additionally, mediation analysis was employed to explore the potential mediating roles of iron status and inflammation in the associations between these metals and anemia., Results: Increased risks of anemia were positively associated with Co and Ni levels but negatively correlated with Se and Mn levels (all with p < 0.05). The trace metal mixture was negatively associated with anemia, with the highest weights of Co and Se in different directions in both the QGC and BKMR models. In the sex-specific analysis, we observed less pronounced protective effects from trace metals in females. Moreover, the mediating proportion of the iron status and inflammation in these relationships ranged from 10.29% to 58.18%., Conclusion: Our findings suggest that the trace element mixture was associated with decreased anemia risk, among which Se was a protective factor while Co was a risk factor, and females were more susceptible. The effects of these trace metals on anemia may be mediated by the iron status and inflammation.

Computer-aided ultrasound (US) imaging is an important prerequisite for early clinical diagnosis and treatment. Due to the harsh ultrasound (US) image quality and the blurry tumor area, recent memory-based video object segmentation models (VOS) achieve frame-level segmentation by performing intensive similarity matching among the past frames which could inevitably result in computational redundancy. Furthermore, the current attention mechanism utilized in recent models only allocates the same attention level among whole spatial-temporal memory features without making distinctions, which may result in accuracy degradation. In this paper, we first build a larger annotated benchmark dataset for breast lesion segmentation in ultrasound videos, then we propose a lightweight clip-level VOS framework for achieving higher segmentation accuracy while maintaining the speed. The Inner-Outer Clip Retformer is proposed to extract spatialtemporal tumor features in parallel. Specifically, the proposed Outer Clip Retformer extracts the tumor movement feature from past video clips to locate the current clip tumor position, while the Inner Clip Retformer detailedly extracts current tumor features that can produce more accurate segmentation results. Then a Clip Contrastive loss function is further proposed to align the extracted tumor features along both the spatial-temporal dimensions to improve the segmentation accuracy. In addition, the Global Retentive Memory is proposed to maintain the complementary tumor features with lower computing resources which can generate coherent temporal movement features. In this way, our model can significantly improve the spatial-temporal perception ability without increasing a large number of parameters, achieving more accurate segmentation results while maintaining a faster segmentation speed. Finally, we conduct extensive experiments to evaluate our proposed model on several video object segmentation datasets, the results show that our framework outperforms state-of-theart segmentation methods.

Patients with cirrhosis face a heightened risk of complications, underscoring the importance of identification. We have developed a Connectome strategy that combines metabolites with peptide spectral matching (PSM) in proteomics to integrate metabolomics and proteomics, identifying specific metabolites bound to blood proteins in cirrhosis using open search proteomics methods. Analysis methods including Partial Least Squares Discriminant Analysis (PLS-DA), Uniform Manifold Approximation and Projection (UMAP), and hierarchical clustering were used to distinguish significant differences among the Cirrhosis group, Chronic Hepatitis B (CHB) group, and Healthy group. In this study, we identified 81 cirrhosis-associated connectomes and established an effective model distinctly distinguishing cirrhosis from chronic hepatitis B and healthy samples, confirmed by PLS-DA, hierarchical clustering analysis, and UMAP analysis, and further validated using six new cirrhosis samples. We established a Unified Indicator for Identifying cirrhosis, including tyrosine, Unnamed&#95;189.2, thiazolidine, etc., which not only enables accurate identification of cirrhosis groups but was also further validated using six new cirrhosis samples and extensively supported by other cirrhosis research data (PXD035024). Our study reveals that characteristic cirrhosis connectomes can reliably distinguish cirrhosis from CHB and healthy groups. The established unified cirrhotic indicator facilitates the identification of cirrhosis cases in both this study and additional research data.

Aims: To evaluate the visual function and foveal architecture in patients with stage 3 idiopathic epiretinal membrane (iERM)., Methods: A cross-sectional observational study included 56 eyes of 52 patients with stage 3 iERM. The patients were classified into type A ectopic inner foveal layers (EIFL) and type B EIFL based on the presence of a continuous hyporeflective band. Visual function and foveal microarchitecture were assessed in enrolled eyes. Best-corrected visual acuity (BCVA), metamorphopsia scores, retinal sensitivity and optical coherence tomography (OCT)/OCT angiography features were compared between two subtypes., Result: The BCVA in type A EIFL and type B EIFL was 0.22 logarithm of minimal angle of resolution (logMAR) (0.15 logMAR, 0.40 logMAR) and 0.53±0.23 logMAR, respectively (p=0.002). Type B EIFL had higher average metamorphopsia scores, especially horizontal metamorphopsia scores, than type A (p=0.013, p=0.007, respectively). Type B EIFL had worse central 2° foveal sensitivity than type A (p=0.034). Type B EIFL had thicker central foveal thickness and EIFL thickness (514.08±73.80 µm vs 444.41±56.57 µm, p=0.001; 159.75±78.30 µm vs 48.44±18.37 µm, p<0.0001; respectively). The foveal avascular zone area of type B EIFL was smaller than that of type A (0.042±0.022 mm 2 vs 0.077±0.039 mm 2 , p<0.0001). The vessel density and flow area of the superficial vascular complex in type B EIFL were larger than those in type A (both p=0.001)., Conclusions: Type B EIFL demonstrated significantly worse visual function than type A EIFL, along with marked differences in foveal microstructure and microvasculature. Our study complements the current staging of iERM and helps determine the optimal timing of iERM surgery., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Liver diseases pose significant challenges to global public health. In the realm of drug discovery and development, overcoming 'on-target off-tissue' effects remains a substantial barrier for various diseases. In this study, we have pioneered a Liver-Targeting Chimera (LIVTAC) approach using a proteolysis-targeting chimera (PROTAC) molecule coupled to the liver-specific asialoglycoprotein receptor (ASGPR) through an innovative linker attachment strategy for the precise induction of target protein degradation within the liver. As a proof-of-concept study, we designed XZ1606, a mammalian bromodomain and extra-terminal domain (BET)-targeting LIVTAC agent, which not only demonstrated enduring tumor suppression (over 2 months) in combination with sorafenib but also an improved safety profile, notably ameliorating the incidence of thrombocytopenia, a common and severe on-target dose-limiting toxic effect associated with conventional BET inhibitors. These encouraging results highlight the potential of LIVTAC as a versatile platform for addressing a broad spectrum of liver diseases., Competing Interests: Declaration of competing interest X.Z., Y.H., C.C., Y.P., and X.Y. are inventors of a pending patent application for the development of LIVTACs for the treatment of liver diseases including HCC., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Diabetic nephropathy (DN) is one of microvascular complication associated with diabetes. Circular RNAs (circRNAs) have been shown to be involved in DN pathogenesis. Hence, this work aimed to explore the role and mechanism of circ&#95;Arf3 in DN. Mouse mesangial cells (MCs) cultured in high glucose (HG) condition were used for functional analysis. Cell proliferation was determined using 5-ethynyl-2'-deoxyuridine (EdU) and cell counting kit-8 assays. Western blotting was used to measure the levels of proliferation indicator PCNA and fibrosis-related proteins α-smooth muscle actin (α-SMA), collagen I (Col I), fibronectin (FN), and collagen IV (Col IV). The binding interaction between miR-107-3p and circ&#95;Arf3 or Tmbim6 (transmembrane BAX inhibitor motif containing 6) was confirmed using dual-luciferase reporter and pull-down assays. Circ&#95;Arf3 is a stable circRNA, and the expression of circ&#95;Arf3 was decreased after HG treatment in MCs. Functionally, ectopic overexpression of circ&#95;Arf3 protected against HG-induced proliferation and elevation of fibrosis-related proteins in MCs. Mechanistically, circ&#95;Arf3 directly bound to miR-107-3p, and Tmbim6 was a target of miR-107-3p. Further rescue assay showed miR-107-3p reversed the protective action of circ&#95;Arf3 on MCs function under HG condition. Moreover, inhibition of miR-107-3p suppressed HG-induced proliferation and fibrosis, which were attenuated by Tmbim6 knockdown in MCs. CircRNA Arf3 could suppress HG-evoked mesangial cell proliferation and fibrosis via miR-107-3p/Tmbim6 axis, indicating the potential involvement of this axis in DN progression., (© 2024. The Author(s).)

Lappanolides A-N (1-14), 14 undescribed sesquiterpenoids, along with 23 known ones (15-37), were isolated from the roots of Saussurea costus, which were primarily categorized into eudesmane, guaiane, and germacrane types. Lappanolide A (1) possessed an unprecedented pseudo-disesquiterpenoids. Their structures and absolute configurations were established using physical data analyses (HRESIMS, IR, 1D and 2D NMR) and ECD calculations. All isolated compounds were tested for anti-hepatitis B virus (anti-HBV) activity. Ten compounds (1, 9, 11, 12, 19, 22, 28, 29, 31, and 36) exhibited activities against HBsAg secretions as determined by ELISA assay, with IC 50 values ranging from 5.2 to 45.7 μM. In particular, compounds 28 and 29 showed inhibition of HBsAg secretion with IC 50 values of 5.28 and 5.30 μM, and CC 50 values of 9.85 and 6.37 μM, respectively, though they all exhibited low selectivity. Several compounds displayed cytotoxicity in the MTT assay. Among them, compound 28 was the most notable and was chosen for further study using flow cytometry. The result showed that it significantly induced HepG2 cell arrest in the S phase and induced apoptosis., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Dexmedetomidine (DEX) has been confirmed to exert neuroprotective effects in various nerve injury models by regulating ferroptosis, including spinal cord injury (SCI). Although it has been established that CDGSH iron sulfur domain 2 (CISD2) can regulate ferroptosis, whether DEX can regulate ferroptosis by CISD2 in SCI remains unclear. Lidocaine was used to induce PC12 cells and stimulate rats to establish SCI models in vitro and in vivo. MTT assays were performed to analyze cell viability. Ferroptosis was assessed by determining the levels of cellular reactive axygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and Fe 2+ . Ferritinophagy was analyzed by LysoTracker staining, FerroOrange staining, and immunofluorescence. Western blotting was carried out to quantify the levels of several proteins. Fluorescence microscopy was also used to observe cell autophagy. The morphology of mitochondria within the tissue was observed under transmission electron microscopy (TEM). DEX treatment weakened lidocaine-induced elevation of ROS, Fe 2+ , and MDA and reduced GSH in PC12 cells, indicating that DEX treatment weakened lidocaine-induced ferroptosis in PC12 cells. Similarly, lidocaine promoted autophagy, Fe 2+ , and microtubule-associated protein 1 light chain 3 (LC3) in PC12 cells and suppressed ferritin and p62 protein levels, indicating that DEX could weaken lidocaine-induced ferritinophagy in PC12 cells. DEX treatment improved the BBB score, reduced tissue damage, increased the number of neurons, and alleviated mitochondrial damage by inhibiting ferroptosis and ferritinophagy in lidocaine-induced SCI rat models. The decreased CISD2, ferritin heavy chain 1 (FTH1), solute carrier family 7-member 11-glutathione (SLC7A11), and glutathione peroxidase 4 (GPX4) protein levels and the elevated nuclear receptor coactivator 4 (NCOA4) protein levels in rat models in the lidocaine group were weakened by DEX treatment. Moreover, CISD2 inhibition reversed the inhibitory effects of DEX treatment on lidocaine-induced ferroptosis and ferritinophagy in PC12 cells significantly. Taken together, DEX treatment could impair lidocaine-induced SCI by inhibiting ferroptosis and ferritinophagy by upregulating CISD2 in rat models., (© 2024. The Author(s).)

Previous evidence on heatwaves' impact on mental health outpatient visits is limited, especially uncertainty on how different heatwave definitions affect this relationship. In this time-series study, we assessed the association between heatwaves and outpatient visits for mental disorders in Guangzhou, China. Daily outpatient visits for mental disorders and its specific categories (schizophrenia, mood, and neurotic disorders) were sourced from the Urban Resident-based Basic Medical Insurance (URBMI) and the Urban Employee-based Basic Medical Insurance (UEBMI) claims databases in Guangzhou from 2010 to 2014. The study employed nine heatwave definitions, based on combinations of three daily mean temperature thresholds (90th, 92.5th, and 95th percentiles) and durations (2, 3, and 4 days). Using quasi-Poisson generalized linear models (GLMs), we estimated the risks (at lag 0 day) and cumulative effects (lag 0-10 days) of heatwaves on mental disorder outpatient visits. Age, gender, types of medical insurance were considered as potential effect modifiers. We observed a positive association between heatwaves and increased total outpatient visits for mental disorders, both at lag 0 day and during lag 0-10 days. The impact of heatwave was significant at lag 0 day for schizophrenia, mood and neurotic disorders visits, it remained significant for neurotic and mood disorders visits during lag 0-10 days. Heatwave durations lasting more than 4 days were associated with higher relative risks of mental disorders at lag 0 day. Older adults had relatively higher effect estimations than younger individuals. This research highlights the effects of extreme heat on mental health., Competing Interests: The authors declare no conflicts of interest relevant to this study., (© 2024 The Author(s). GeoHealth published by Wiley Periodicals LLC on behalf of American Geophysical Union.)

The landscape of pharmacological treatment for Alzheimer's disease (AD) has undergone significant transformations with the advent of disease-modifying therapies (DMTs) targeting β-Amyloid (Aβ) accumulation, one of the hallmark pathologies of AD. The approval and market introduction of monoclonal antibodies mark the dawn of a new era in AD therapeutics as well. Furthermore, considerable progress has also been made in the development of new drugs targeting non-Aβ and non-Tau protein pathways. These advancements are key in tackling the root causes of AD, offering hope for treatments that both relieve symptoms and slow disease progression, improving patient outcomes and quality of life. This review aims to provide a comprehensive update on the advances in drug development and application for AD, including those currently in clinical trials and those already approved for the market to treat patients.

Shade has a direct impact on photosynthesis and production of plants. Exposure to shade significantly reduces crops yields. Identifying shade-tolerant genomic loci and soybean varieties is crucial for improving soybean yields. In this study, we applied a shade treatment (30% light reduction) to a natural soybean population consisting of 264 accessions, and measured several traits, including the first pod height, plant height, pod number per plant, grain weight per plant, branch number, and main stem node number. Additionally, we performed GWAS on these six traits with and without shade treatment, as well as on the shade tolerance coefficients (STCs) of the six traits. As a result, we identified five shade-tolerance varieties, 733 SNPs and four candidate genes over two years. Furthermore, we developed four kompetitive allele-specific PCR (KASP) makers for the STC of S18&#95;1766721, S09&#95;48870909, S19&#95;49517336, S18&#95;3429732. This study provides valuable genetic resources for breeding soybean shade tolerance and offers new insights into the theoretical research on soybean shade tolerance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jia, Hu, Li, Wei, Wang, Zhang, Zhang, Liu, Chen, Wang and Chen.)

Fueled by the rapid advancement of nanofabrication, metasurface has provided unprecedented opportunities for 3D holography. Large depth 3D meta-holography not only greatly increases information storage capacity, but also enables distinguishing of the relative spatial relationship of 3D objects, which has important applications in fields like optical information storage and medical diagnosis. Although the methods based on Fresnel diffraction theory can reconstruct the real depth information of 3D objects, the maximum depth is only 2 mm. Here, we develop a 3D meta-holography based on angular spectrum diffraction theory to break through the depth limit. By developing the angular spectrum diffraction theory into meta-holography, the metasurface structure with independent polarization control is used to create a polarization multiplexing 3D meta-hologram. The fabricated amorphous silicon metasurface increases the depth range by 47.5 times and realizes 0.95 dm depth reconstruction for polarization independent and different color 3D meta-hologram in visible. Such polarization controlled large-depth color meta-holography is expected to open avenue for data storage, display, information security and virtual reality., (© 2024. The Author(s).)

Ganoderma has received much attention for its medicinal value, but the manipulation of multiple genes remains a challenge, hindering the genetic engineering of this species for the development of cell factories. Here, we first showed that the presence of an intron is necessary for the efficient expression of the endogenous cDNA of carboxin-resistant gene (cbx) in G. lucidum. Then, the self-cleaving function of 2 A peptide was investigated in G. lucidum by linking cbx cDNA to the codon-optimized hygromycin B-resistant gene (ophph) using the 2A-peptide sequence. The results showed that cbx cDNA and ophph can be successfully expressed in G. lucidum in a bicistronic manner from a single transcript. Moreover, the expression of both genes was not affected by the order within the 2 A cassette. In addition, simultaneous expression of cbx cDNA, ophph, and codon-optimized yellow fluorescent protein gene (opyfp) was conducted for the first time in G. lucidum using the 2 A peptide-based approach. The developed method was successfully applied to express both cDNA of the 3-hydroxy-3-methylglutaryl coenzyme A reductase (hmgr) and squalene epoxidase gene (se) for enhanced production of ganoderic acids (GAs) in G. lucidum. The engineered strain produced the maximum content of GA-Mk, GA-T, GA-S, and GA-Me were 26.56±3.53,39.58±3.75, 16.54±2.16, and 19.1±1.87 μg/100 mg dry weight, respectively. These values were 3.85-, 4.74-, 3.65-, and 3.23-fold higher than those produced by the control strain. The developed method will be useful for the manipulation of complex metabolic or regulatory pathways involving multiple genes in Ganoderma., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Comprehensive chromosomal status of blastocyst from women with polycystic ovary syndrome (PCOS) was limited. This study aimed to identify possible differences in the preimplantation blastocyst chromosome aberrations between PCOS women and controls receiving preimplantation genetic testing (PGT)., Methods: This was a multi-center retrospective cohort study including a total of 707 blastocysts from 147 PCOS women and 3006 blastocysts from 821 control women receiving PGT between 2015 and 2021. Embryonic chromosomal aberration spectrums were compared between PCOS and controls. Mixed effects generalized linear model was conducted to explore possible influence of PCOS-related endocrinological disorders on embryonic chromosomal abnormalities., Results: Blastocysts from PCOS demonstrated significantly lower aneuploidy rate (15.2% vs. 25.2% per women, P < 0.001; 14.7% vs. 25.4% per blastocyst, P < 0.001) but greater mosaicism rate (12.5% vs. 8.0% per women, P = 0.007; 16.5% vs. 8.7% per blastocyst, P < 0.001). Mixed effects generalized linear model identified PCOS as an independent protective factor against embryonic aneuploidy (adjusted odds ratio = 0.68, 95% confidence interval, 0.50-0.93, P = 0.014) but a risk factor for embryonic mosaicism (adjusted odds ratio = 1.52, 95% confidence interval 1.11-2.10, P = 0.009). Further model analysis suggested that insulin resistance could be responsible for the increased risk of embryonic mosaicism among PCOS women (adjusted odds ratio = 2.17, 95% confidence interval, 1.10-4.31, P = 0.026)., Conclusion: PCOS is associated with a lower aneuploidy risk but an increased mosaicism risk in preimplantation blastocysts, and insulin resistance should be investigated as a potential cause., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The Chang'E-6 (CE-6) mission successfully achieved return of the first samples from the far side of the Moon. The sampling site of CE-6 is located in the South Pole-Aitken (SPA) basin-the largest, deepest and oldest impact basin on the Moon. The 1935.3 g of CE-6 lunar samples exhibit distinct characteristics compared with previous lunar samples. This study analyses the physical, mineralogical, petrographic and geochemical properties of CE-6 lunar scooped samples. The CE-6 soil has a significantly lower bulk density (0.983 g/cm 3 ) and true density (3.035 g/cm 3 ) than the Chang'E-5 (CE-5) samples. The grain size of the CE-6 soil exhibits a bimodal distribution, indicating a mixture of different compositions. Mineralogically, the CE-6 soil consists of 32.6% plagioclase (anorthite and bytownite), 19.7% augite, 10% pigeonite and 3.6% orthopyroxene, and with low content of olivine (0.5%) but high content of amorphous glass (29.4%). Geochemically, the bulk composition of CE-6 soil is rich in Al 2 O 3 (14%) and CaO (12%) but low in FeO (17%), and trace elements of CE-6 soil such as K (∼630 ppm), U (0.26 ppm), Th (0.92 ppm) and rare-earth elements are significantly lower than those of the lunar soils within the Procellarum KREEP Terrane. The local basalts are characterized by low-Ti (TiO 2 , 5.08%), low-Al (Al 2 O 3 9.85%) and low-K (∼830 ppm), features suggesting that the CE-6 soil is a mixture of local basalts and non-basaltic ejecta. The returned CE-6 sample contains diverse lithic fragments, including local mare basalt, breccia, agglutinate, glasses and leucocrate. These local mare basalts document the volcanic history of the lunar far side, while the non-basaltic fragments may offer critical insights into the lunar highland crust, SPA impact melts and potentially the deep lunar mantle, making these samples highly significant for scientific research., (© The Author(s) 2024. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

Objective: To study the effectiveness and safety of abdominal active balloon closure during cesarean sections for patients with pernicious placenta previa (PPP)., Methods: A retrospective analysis was conducted on 140 patients with PPP and placenta accreta who were hospitalized and gave birth at the Third Affiliated Hospital of Zhengzhou University from June 2022 to December 2023. The patients were divided into two groups based on whether intervention was applied. The intervention group [intraoperative abdominal aortic balloon occlusion (IAABO) group] included 118 patients who received prophylactic abdominal aortic balloon occlusion during cesarean section. The routine group, without balloon occlusion, consisted of 22 patients., Results: Compared to the routine group, the IAABO group had significantly lower intraoperative blood loss, blood transfusion volume, and hysterectomy rate (all P<0.05). Additionally, the IAABO group showed lower postoperative pain scores, shorter ambulation time, and higher patient satisfaction (all P<0.05). The neonatal intensive care unit admission rate and incidence of complications were also significantly lower in the IAABO group (both P<0.05)., Conclusion: Abdominal aortic balloon closure during cesarean sections can reduce bleeding and the need for blood transfusions in cases of PPP, thereby lowering the hysterectomy rate and the incidence of related complications., Competing Interests: None., (AJTR Copyright © 2024.)

Inflammation induces tumor formation and plays a crucial role in tumor progression and prognosis. KCNK6, by regulating K(+) efflux to reduce NLRP3 Inflammasome-induced lung injury, relaxes the aorta. This study aims to elucidate the effects and biological mechanism of KCNK6 in inflammation-associated carcinogenesis, which may be essential for colon homeostasis and the defense system. To induce colitis, mice were given 3.0% Dextran Sodium Sulfate (DSS) in their drinking water for 7 days. The Azoxymethane (AOM) +DSS method was used to induce colon cancer in the mice model. Bone marrow-derived macrophages (BMDM) from Kcnk6-/- mice, AW264.7 cells, and human colon cancer HCT116 and Caco2 cells were used as in vitro models. The loss of Kcnk6 prevented spontaneous colitis and restored mucosal integrity and homeostatic molecules. Additionally, the loss of Kcnk6 reduced the severity of AOM/DSS-induced carcinogenesis. Kcnk6 promoted cell viability and proliferation in HCT-116 or Caco-2 cells. The loss of Kcnk6 inhibited the levels of inflammatory factors in BMDM cells. Kcnk6 accelerated potassium channel activity, inducing NLRP3 inflammasome activation. METTL3-mediated m6A modification increased Kcnk6 stability in a YTHDF2-dependent manner. Histone lactylation activated the transcription of YTHDF2/Kcnk6. Our study revealed the important role of Kcnk6 in inflammation-associated carcinogenesis progression. The m6A methyltransferase METTL3 and histone lactylation increased Kcnk6 stability in a YTHDF2-dependent manner, providing a potential strategy for inflammation-associated carcinogenesis or colorectal cancer therapy.

Retinal neovascular disease is a leading cause of vision loss and blindness globally. It occurs when abnormal new blood vessels form in the retina. In this study, we utilized tetrahedral framework nucleic acids (tFNAs) as vehicles to load quercetin (QUE), a small-molecule flavonoid, forming a deoxyribonucleic acid (DNA) nanocomplex, tFNAs-QUE. Our data show this nanocomplex inhibits pathological neovascularization, reduces the area of retinal nonperfusion area, protects retinal neurons, and preserves the visual function. Further, we discovered that tFNAs-QUE selectively upregulates the AKT/Nrf2/HO-1 signaling pathway, which can suppress pathological vascular growth and exert antioxidative effects. Therefore, this study presents a promising small-molecule-loading mechanism for the treatment of ischemic retinal diseases.

Partial nitrification (PN) is a prerequisite step for the short-cut nitrogen removal process, which is crucial to provide stable nitrite accumulation for subsequent units. The present study innovatively proposed a new strategy for the rapid establishment of PN by adopting short-term anoxic starvation combined with high free ammonia inhibition. The sludge obtained from the secondary sedimentation tank of a municipal wastewater treatment plant was starved for 7 days under anoxic conditions, and then wastewater with high ammonia nitrogen (400 mg L -1 ) was introduced. Within 17 days, stable nitrite accumulation was achieved in the sequencing batch reactor, and the nitrite accumulation rate reached more than 95.0%. The activity of ammonia monooxygenase enzyme increased from 0.0364 ± 0.0074 to 0.1275 ± 0.0021 μg NO 2 - -N·mg -1 protein min -1 , while that of hydroxylamine oxidoreductase enzyme increased from 1.5350 ± 0.0208 to 6.3852 ± 0.0400 EU g -1 SS. The relative abundance of Nitrosomonas increased from 0.10% to 25.90%, while that of Nitrospira consistently remained below 0.04%. And the relative abundance of short-cut denitrifying bacteria, including Truepera , OLB8 , and OLB13 all increased. The results proved that the short-term anoxic starvation combined with high free ammonia inhibition was an effective strategy for rapid establishment of PN.

As proactivity becomes vital for organizational success, retaining proactive employees becomes increasingly important, making the relationship between a proactive personality and turnover intention a key research topic. While existing studies have largely depicted turnover as a consequence of dissatisfaction and have identified negative indirect relationships, this study seeks to challenge that perspective by proposing that, in today's boundaryless career environment, people also engage in voluntary turnover for career advancement. Using a self-regulation career management model, we propose that proactive employees set ambitious career goals influenced by career aspirations, leading them to seek external opportunities and thus exhibit higher turnover intention. However, when organizations implement career management practices, this relationship weakens as proactive employees perceive opportunities to achieve their goals within their current organizations. We tested these hypotheses with a sample of 342 respondents using the SPSS macro PROCESS. The findings support our propositions, revealing a positive indirect effect through career aspirations, which diminishes when perceived organizational career management is strong.

All-terrain microrobots possess significant potential in modern medical applications due to their superior maneuverability in complex terrains and confined spaces. However, conventional microrobots often struggle with adaptability and operational difficulties in variable environments. This study introduces a magnetic torque-driven all-terrain multiped microrobot (MTMR) to address these challenges. By coupling the structure's multiple symmetries with different uniform magnetic fields, such as rotating and oscillating fields, the MTMR demonstrates various locomotion modes, including rolling, tumbling, walking, jumping, and their combinations. Experimental results indicate that the robot can navigate diverse terrains, including flat surfaces, steep slopes (up to 75°), and gaps over twice its body height. Additionally, the MTMR performs well in confined spaces, capable of passing through slits (0.1 body length) and low tunnels (0.25 body length). The robot shows potential for clinical applications like minimally invasive hemostasis in internal bleeding and thrombus removal from blood vessels through accurate cargo manipulation capability. Moreover, the MTMR can carry temperature sensors to monitor environmental temperature changes in real time while simultaneously manipulating objects, displaying its potential for in-situ sensing and parallel task implementation. This all-terrain microrobot technology demonstrates notable adaptability and versatility, providing a solid foundation for practical applications in interventional medicine., (© 2024 Wiley‐VCH GmbH.)

Natural enzymes are able to function effectively under optimal physiological conditions, but the intrinsic performance often fails to meet the demands of industrial production. Existing strategies are based mainly on the evaluation and subsequent combination of single-point mutations; however, this approach often suffers from a limited number of designable residues and from low accuracy. Here, we propose a strategy (Co-MdVS) based on coevolutionary analysis and multidimensional virtual screening for precise design to improve enzyme robustness, employing nattokinase as a model. Using this strategy, we efficiently screened 8 dual mutants with enhanced thermostability from a virtual mutation library containing 7980 mutants. After further iterative combination, the optimal mutant M6 exhibited a 31-fold increase in half-life at 55 °C, significantly enhanced acid resistance, and improved catalytic efficiency with different substrates. Molecular dynamics simulations indicated that the reduced flexibility of thermal and acid-sensitive regions resulted in a significantly increased robustness of M6. Furthermore, the potential of multidimensional virtual screening in enhancing design precision has been validated on l-rhamnose isomerase and PETase. Therefore, the Co-MdVS strategy introduced in this research may offer a viable approach for developing enzymes with enhanced robustness., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by complex pathogenesis mechanisms. Among these, β-amyloid plaques and hyperphosphorylated Tau protein tangles have been identified as significant contributors to neuronal damage. This study investigates thonningianin A (TA) from Penthorum chinense Pursh (PCP) as a potential inhibitor targeting these pivotal proteins in AD progression. The inhibitory potential of PCP and TA on Aβ fibrillization was initially investigated. Subsequently, ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry and biolayer interferometry were employed to determine TA's affinity for both Aβ and Tau. The inhibitory effects of TA on the levels and cytotoxicity of AD-related proteins were then assessed. In 3xTg-AD mice, the therapeutic potential of TA was evaluated. Additionally, the molecular interactions between TA and either Aβ or Tau were explored using molecular docking. We found that PCP-total ethanol extract and TA significantly inhibited Aβ fibrillization. Additionally, TA demonstrated strong affinity to Aβ and Tau, reduced levels of amyloid precursor protein and Tau, and alleviated mitochondrial distress in PC-12 cells. In 3xTg-AD mice, TA improved cognition, reduced Aβ and Tau pathology, and strengthened neurons. Moreover, molecular analyses revealed efficient binding of TA to Aβ and Tau. In conclusion, TA, derived from PCP, shows significant neuroprotection against AD proteins, highlighting its potential as an anti-AD drug candidate., (© 2024 John Wiley & Sons Ltd.)

Background: Declining total fertility rates have been observed in low- and middle-income countries (LMICs). However, it remains unclear if this trend is related to a reduction in fecundity of general population. Research evidence on contributing factors to fecundity reduction is also limited. We aimed to first estimate couple fecundity in LMICs and then investigate its association with ambient particulate matter (PM) exposure., Methods: Using the information from Demographic and Health Surveys between 2003 and 2019, we estimated median time to pregnancy (TTP) and infertility prevalence across 30 LMICs, by employing a current duration approach. Individual PM (PM 1 , PM 2.5 , and PM 10 ) exposure during the period of 'at risk' of pregnancy was assessed by months. An accelerated failure model was used to elucidate the association between monthly time-varying PM exposure and TTP. Subsequently, we estimated the prolonged TTP attributable to PM exposures above the World Health Organization (WHO)'s recommended air quality level in 2021., Results: Within the study regions, median TTP ranged from 6.90 (95 % CI 6.02-7.87) months in Latin America & Caribbean to 10.29 (95 % CI 9.28-11.36) months in East Asia & Pacific, with corresponding infertility prevalence varying from 33 % (95 % CI 29 %-36 %) to 44 % (95 % CI 41 %-48 %). Our estimations indicated that TTP was 1.08 (95 % CI: 0.99-1.18), 1.12 (95 % CI 1.06-1.19), and 1.05 (95 % CI 1.03-1.07) times longer for every 10 μg/m 3 increment in PM 1 , PM 2.5 , and PM 10 , respectively. The prolonged TTP attributable to PM exposures surpassing the WHO guideline ranged from 0.11 to 2.81 months across the studied regions., Discussion: Ambient particulate matter is identified as a potential contributing factor to impaired fecundity in general population of LMICs. The findings underscore the importance of coordinated efforts to control ambient air pollution to mitigate the risk of fecundity reduction among the general population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Endocrine disruptors such as bisphenol A (BPA) adversely affect the environment and human health. Laccases are used for the efficient biodegradation of various persistent organic pollutants in an environmentally safe manner. However, the direct application of free laccases is generally hindered by short enzyme lifetimes, non-reusability, and the high cost of a single use. In this study, laccases were immobilized on a novel magnetic three-dimensional poly(ethylene glycol) diacrylate (PEGDA)-chitosan (CS) inverse opal hydrogel (LAC@MPEGDA@CS@IOH). The immobilized laccase showed significant improvement in the BPA degradation performance and superior storage stability compared with the free laccase. 91.1% of 100 mg/L BPA was removed by the LAC@MPEGDA@CS@IOH in 3 hr, whereas only 50.6% of BPA was removed by the same amount of the free laccase. Compared with the laccase, the outstanding BPA degradation efficiency of the LAC@MPEGDA@CS@IOH was maintained over a wider range of pH values and temperatures. Moreover, its relative activity of was maintained at 70.4% after 10 cycles, and the system performed well in actual water matrices. This efficient method for preparing immobilized laccases is simple and green, and it can be used to further develop ecofriendly biocatalysts to remove organic pollutants from wastewater., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Objectives: Low muscle mass (MM) is significant in cancer patients, and computed tomography (CT) is considered the reference standard for MM assessment. We investigated the consistency of CT and multifrequency bioelectrical impedance analysis (mBIA) in detecting body composition at baseline and during anticancer treatment and the relationship between MM and malnutrition as well as complications in lung and cervical cancer patients., Methods: Abdominal CT and mBIA were conducted to assess body composition at baseline for all patients and repeated for patients with cervical cancer after 4 wk of chemoradiotherapy. Concordance was compared by intraclass correlation coefficient and Bland-Altman plots. Receiver operating characteristic analysis was used to assess the diagnostic efficacy of mBIA for low MM. Correlation analysis was conducted to assess the relationship between MM and Nutritional Risk Screening 2002 and Global Leadership Initiative on Malnutrition. Furthermore, we assessed whether there was a difference in the incidence of chemoradiotherapy side effects in the low MM group derived by CT or mBIA., Results: A total of 77 cervical and 73 lung cancer patients were enrolled. mBIA showed fair discriminative capacity (area under the curve = 0.651) for detecting low MM, the concordance of skeletal MM and visceral fat area between CT and mBIA was good (intraclass correlation coefficient = 0.712 and 0.698, respectively), and mBIA and CT had consistent observations of muscle and fat changes (P = 0.051 and 0.124, respectively). There was no difference in the incidence of chemoradiotherapy side effects in the low MM group compared with controls regardless of whether derived by CT or mBIA (P > 0.05). MM was correlated with Nutritional Risk Screening 2002 and Global Leadership Initiative on Malnutrition but showed unsatisfactory prediction of malnutrition (area under the curve <0.7)., Conclusions: mBIA- and CT-derived body composition was highly correlated, and agreement was reached on body composition changes during treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Previous studies revealed that vitamin K might help maintain muscle homeostasis, but this association has received little attention. We aimed to explore the associations of vitamin K intake with skeletal muscle mass and strength., Methods: We included cross-sectional data from the U.S. National Health and Nutrition Examination Survey (NHANES, 2011-2018). Vitamin K intake was assessed via 24-h recall. Covariate-adjusted multiple linear regression and restricted cubic splines were used to evaluate the associations of dietary vitamin K intake with skeletal muscle mass and strength, measured by dual-energy X-ray absorptiometry and handgrip dynamometer, respectively., Results: Dietary vitamin K intake was positively associated with skeletal muscle mass in males (β = 0.05747, p  = 0.0204) but not in females. We also revealed a positive association between dietary vitamin K intake and handgrip strength within the range of 0-59.871 μg/d ( P nonlinear  = 0.049). However, beyond this threshold, increasing vitamin K intake did not cause additional handgrip strength improvements., Conclusion: We provided evidence for a positive relationship between dietary vitamin K intake and skeletal muscle mass in males. Moreover, our study revealed a nonlinear relationship between dietary vitamin K intake and handgrip strength, highlighting an optimal intake range., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Chen, Guo, Wang, Bao, Zhang and Yu.)

Celiac disease, characterized as an autoimmune disorder, possesses the capacity to affect multiple organs and systems. Earlier research has indicated an increased risk of kidney diseases associated with celiac disease. However, the potential causal relationship between genetic susceptibility to celiac disease and the risk of kidney diseases remains uncertain. We conducted Mendelian randomization analysis using nonoverlapping European population data, examining the link between celiac disease and 10 kidney traits in whole-genome association studies. We employed the inverse variance-weighted method to enhance statistical robustness, and results' reliability was reinforced through rigorous sensitivity analysis. Mendelian randomization analysis revealed a genetic susceptibility of celiac disease to an increased risk of immunoglobulin A nephropathy (OR = 1.44; 95% confidence interval [CI] = 1.17-1.78; P = 5.7 × 10-4), chronic glomerulonephritis (OR = 1.15; 95% CI = 1.08-1.22; P = 2.58 × 10-5), and a decline in estimated glomerular filtration rate (beta = -0.001; P = 2.99 × 10-4). Additionally, a potential positive trend in the causal relationship between celiac disease and membranous nephropathy (OR = 1.37; 95% CI = 1.08-1.74; P = 0.01) was observed. Sensitivity analysis indicated the absence of pleiotropy. This study contributes novel evidence establishing a causal link between celiac disease and kidney traits, indicating a potential association between celiac disease and an elevated risk of kidney diseases. The findings provide fresh perspectives for advancing mechanistic and clinical research into kidney diseases associated with celiac disease., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Epidemiological studies linking metabolic syndrome (MetS) and exposure to perfluoroalkyl substances (PFASs) are limited, and the observations gleaned thus far are inconclusive. The study was performed to explore the association of serum PFASs both singly and in a mixed manner with MetS, and meanwhile to examine whether this association was mediated by serum albumin in a US national population., Methods: Total 8108 participants from the National Health and Nutrition Examination Survey, 2007-2018 were included. Four PFASs - including perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluoromethylheptane sulfonic acid (PFOS), and perfluorooctanoic acid (PFOA), were selected. Weighted quantile sum regression was used to evaluate mixed PFAS exposure and MetS. Multivariable logistic regression models were used to calculate odd ratio (OR) and 95 % confidence interval (95 % CI). Mediating analyses were used to evaluate the mediating effects of albumin., Results: Comparing the highest with lowest quartile yielded a multivariable-adjusted OR (95 % CI) of 1.40 (1.14-1.72) for PFHxS, 1.36 (1.09-1.70) for PFNA, 1.26 (1.00-1.58) for PFOA, and 1.50 (1.19-1.88) for PFOS when associating MetS. Per unit increment in ln-transformed PFHxS, PFNA, PFOA, and PFOS concentrations was significantly associated with 16 %, 17 %, 13 %, and 15 % increased risk of MetS, respectively. When stratified by sex, the significant association between four PFASs and MetS was only noted in females. Mixed PFAS exposure was inversely associated with MetS, and 8.1 % of this association was mediated by serum albumin ( P  < 0.001)., Conclusions: Our findings indicate a significant and independent association of serum PFASs with MetS, and importantly this association was dose-dependent, sex-specific, and possibly mediated by serum albumin., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

The development of antibody tracers for positron emission tomography (PET) imaging enables real-time monitoring of tumor expression of programmed cell death ligand 1 (PD-L1) in vivo , aiming to facilitate the selection of immunotherapy responders. However, the slow pharmacokinetics of the antibodies in vivo limits their applications in PET imaging with commonly used radionuclides with short half-lives. In this study, we developed a pretargeted PET imaging strategy based on Diels-Alder (IEDDA) click chemistry to overcome these limitations. Atezolizumab and durvalumab, the most commonly used PD-L1 antibodies in cancer immunotherapy, were selected and compared in the development of the pretargeted PET imaging strategy. Fluorine-18-labeled derivatives of methyl tetrazine ([ 18 F]Tz, [ 18 F]PEG 6 -Tz, and [ 18 F]PEG 12 -Tz) were tested in biodistribution and PET imaging of A549-PDL1 xenografts (PD-L1 positive) pretargeted with the trans-cyclooctene (TCO)-functionalized atezolizumab/durvalumab. The biodistribution and imaging results indicated that atezolizumab-TCO/[ 18 F]PEG 12 -Tz was more suitable for pretargeted PET imaging strategy, and the optimal interval time was 48 h after atezolizumab-TCO administration, where the atezolizumab-TCO/[ 18 F]PEG 12 -Tz pretargeted approach clearly delineated the A549-PDL1 tumor with a tumor-to-muscle ratio of 5.33, while the ratios are 3.39 and 2.39 for durvalumab/[ 18 F]PEG 12 -Tz and mock-pretargeting controls, respectively. In conclusion, a pretargeted 18 F-immuno-PET imaging technology was successfully established on atezolizumab. The high-contrast PET images of the A549-PDL1 tumor models demonstrate that the pretargeting strategy incorporating short-lived fluorine-18 is viable in identifying tumors with high PD-L1 expression, marking this strategy as a potential candidate for further clinical translation., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)